UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Splanchnic artery occlusion (SAO) shock is characterized by irreversible circulatory failure. Tumour necrosis factor (TNF-alpha) may affect the L-arginine/nitric oxide (NO) pathway, thus contributing to the cardiovascular derangements of circulatory shock. 2. We investigated the contribution of both TNF-alpha and the L-arginine/nitric oxide pathway to the vascular dysfunction of SAO shock. Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the coeliac trunk for 45 min developed a severe shock state (SAO shock) resulting in a fatal outcome within 75-90 min after the release of occlusion. Sham operated animals were used as controls. SAO shocked rats had also a marked hypotension and enhanced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats showed a marked hyporeactivity to phenylephrine (PE 1 nM-10 microM) and reduced responsiveness to acetylcholine (ACh 10 nM-10 microM). Endothelium-denuded aortic rings had also a marked hyporeactivity to phenylephrine, which was restored to control values by in vitro administration of NG nitro-L-arginine-methyl ester (L-NAME 10 microM). 3. In vivo administration of cloricromene (2 mg kg-1, i.v.), an inhibitor of TNF-alpha biosynthesis, increased survival, enhanced mean arterial blood pressure and reduced macrophage and serum levels of TNF-alpha. Furthermore, aortic rings from shocked rats treated with cloricromene exhibited a greater contractile response to phenylephrine and improved responsiveness to ACh when compared to aortic rings from vehicle-treated SAO shocked rats. 4. Our results suggest that TNF-alpha alters both endothelial and muscular L-arginine/nitric oxide pathways which in turn produce vascular dysfunction in SAO shock.
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PMID:Participation of tumour necrosis factor and nitric oxide in the mediation of vascular dysfunction in splanchnic artery occlusion shock. 788 68

1. Acetylcholine-induced contractions of the rat isolated anococcygeus muscle were blocked by atropine (0.1 microM), slightly enhanced by hexamethonium (0.1 mM) and tetrodotoxin (1 microM), but little affected by prazosin (0.1 microM). 2. In the presence of the alpha 2-adrenoceptor agonist, UK14304, which raised the tone of the muscle, acetylcholine had a biphasic effect consisting of an initial relaxation followed by a contraction. 3. Atropine (0.1 microM) enhanced the relaxant component and abolished the contractile component of the response, whereas tetrodotoxin, omega-conotoxin GVIA or hexamethonium abolished or greatly reduced the relaxant component. 4. The nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) increased acetylcholine-induced contractions in the absence of UK14304 and markedly reduced the relaxant component to acetylcholine in the presence of UK14304. The effects of L-NAME were annulled by L-arginine (300 microM). 5. The results suggest that acetylcholine acts concurrently on muscarinic receptors of the smooth muscle to cause contraction and nicotinic receptors of nitrergic nerves to cause relaxation. The observed response is the resultant of these two opposing effects and depends also on the prevailing tone.
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PMID:Modulation of acetylcholine-induced contractions of the rat anococcygeus muscle by activation of nitrergic nerves. 790 72

1. Acetylcholine stimulated repolarization and relaxation in isolated segments of rat small mesenteric artery (D100 = 325 +/- 9 microns) in which the smooth muscle cells were depolarized and contracted by submaximal concentrations of noradrenaline (0.75-2.5 microM). There was no significant difference either in the time taken to initiate relaxation or hyperpolarization, or for these parameters to reach maximum in response to acetylcholine. 2. The nitric oxide synthase inhibitor, NG-nitro L-arginine methyl ester (L-NAME, 100 microM) reduced the pD2 for acetylcholine-induced relaxation from 7.5 to 7 and depressed the maximum relaxation from 89% to 68% in tissues stimulated with noradrenaline. The pD2 for smooth muscle repolarization in these experiments was also reduced (7.4 to 6.6) but the maximum change in membrane potential in response to acetylcholine was unaltered. The increase in potential now clearly preceded relaxation by 3.7 s (to initiation) and 4.7 s (to maximum). 3. In the presence of noradrenaline and a raised potassium concentration (25 mM), the repolarization to acetylcholine was markedly attenuated. Simultaneous tension measurements also revealed a marked reduction in the maximal relaxation to acetylcholine, but the pD2 was unchanged at 7.4. 4. The residual relaxation recorded in the absence of marked repolarization (in the presence of noradrenaline and 25 mM potassium) was abolished by the addition of 100 microM L-NAME. 5. Nitric oxide gas in solution (0.2-2.2 microM; NOg) relaxed artery segments precontracted with noradrenaline. The magnitude of relaxation to NOg was not altered in the presence of noradrenaline and 25 mM potassium. 6. These data provide additional evidence that acetylcholine-evoked endothelium-dependent increases in membrane potential provide a major mechanism for smooth muscle relaxation in the mesenteric artery.They also show that voltage-dependent and independent (initiated by NO) mechanisms can both contribute to relaxation, and suggest that NO may modulate the increase in membrane potential or the release of a hyperpolarizing factor.
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PMID:Contribution of both nitric oxide and a change in membrane potential to acetylcholine-induced relaxation in the rat small mesenteric artery. 792 9

We examined the actions of a nitric oxide donor, CAS754, in a rat model of carotid artery intimal injury. Seven days following injury, the injured carotid arteries were studied for endothelial release of nitric oxide (NO) and for histological measurement of the intimal/medial (I/M) ratio. Basal release of NO was assessed by NG-nitro-L-arginine methyl ester (L-NAME)-induced vasocontraction. L-NAME contracted injured rat carotid artery rings about 27% of that obtained in control rats (p < 0.01). However, CAS754 given at 30 mcg/day i.v. resulted in a L-NAME contraction of twice that of vehicle-treated rats (p < 0.01). A control compound lacking the NO moiety (C-3934) yielded a contraction to L-NAME comparable to untreated injured rats. We also tested the ability of rat carotid artery rings to relax to the endothelium-dependent vasodilators, acetylcholine and A23187. ACh (10 mcM) relaxed carotid artery rings only about 20% of control values in vehicle-treated and in C-3934-treated rats, compared with a vasorelaxation of over 80% of control in CAS754-treated rats (p < 0.01). Relaxation to acidified NaNO2 (100 mcM) was not significantly different among any of the groups of carotid arteries, indicating normal vascular smooth muscle responses following intimal injury. Morphometric assessment of carotid arteries isolated from injured rats given either vehicle or C-3934 showed marked intimal thickening with an average intimal/medial (I/M) ratio of 0.79 +/- 0.05 and 0.73 +/- 0.06, respectively, compared with 0.10 +/- 0.02 in non-injured arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelial preserving actions of a nitric oxide donor in carotid arterial intimal injury. 793 13

1. The effect of endogenous and exogenous nitric oxide on the membrane potential (Em) of smooth muscle cells of the thoracic aorta of rats was investigated. 2. In tissues with intact endothelium, application of ACh or carbachol generated a change of the membrane potential consisting of an initial hyperpolarization by 10-12 mV, followed by a partial recovery toward a level which was at 10 min still 6-8 mV more negative than in control conditions. 3. Application of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of endogenous NO production, had no significant effect on the resting membrane potential. The initial peak endothelium-dependent hyperpolarization elicited by ACh or carbachol was not significantly diminished. However, the recovery was more accentuated. Similarly, NG-monomethyl-L-arginine (L-NMMA) significantly diminished the second component of the endothelium-dependent hyperpolarization without affecting the magnitude of the first transient peak Em change. 4. Nitroglycerin produced a small sustained hyperpolarization of 1-2 mV, and the NO donor SIN-1, the active metabolite of molsidomine, similarly increased Em by about 1 mV. Infusion of high doses of acidified NaNO2 solution caused a hyperpolarization smaller than that evoked by ACh or carbachol. 5. 8-Bromo-cyclic GMP caused little change of membrane potential. In the presence of 8-Br-cGMP, ACh evoked a membrane electrical response similar to that observed in the absence of the nucleotide. 6. It is concluded that, in the rat aorta, the initial peak endothelium-dependent hyperpolarization observed under the influence of ACh or carbachol is not directly related to the synthesis of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of nitric oxide to the endothelium-dependent hyperpolarization in rat aorta. 802 34

1. The role played by nitric oxide (NO) in the regulation of blood flow to the canine isolated hemidiaphragm was evaluated by determining (a) the effects of the L-arginine analogues NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-L-arginine (L-NOARG), and argininosuccinic acid (ArgSA) on baseline vascular resistance and of the latter two agents on endothelium-dependent (acetylcholine, ACh) and endothelium independent (sodium nitroprusside, SNP) vasodilatation; (b) the effects of L- and D-arginine on baseline vascular resistance; and (c) the effects of L-glutamine, an inhibitor of intracellular recycling of L-citrulline to L-arginine, on baseline resistance and on the response to ACh and SNP. 2. L-NAME, L-NOARG and ArgSA (6 x 10(-4) M final concentration) increased baseline diaphragmatic vascular resistance to a similar extent (28.6 +/- 4.2%, 26.7 +/- 4.3% and 32.8 +/- 4.6% respectively). L-NOARG and ArgSA reversed the vasodilator effect of ACh but not of SNP. 3. L- and D-arginine had no effect on vascular resistance. 4. L-Glutamine (10(-3) M) increased baseline vascular resistance by 10 +/- 1.9% (P < 0.05) but did not alter responses to either ACh or SNP. 5. Basal NO release plays a role in the regulation of baseline diaphragmatic vascular resistance. L-Arginine analogues tested potently and specifically inhibited this process. Moreover, extracellular L-arginine appears to have no effect on baseline diaphragmatic vascular resistance.
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PMID:Regulation of baseline vascular resistance in the canine diaphragm by nitric oxide. 803 63

We examined the hypothesis that the coronary vasomotor responses to etomidate (ETO), propofol (PRO), and sodium thiopental (STP) are mediated through contrasting effects on the resting nitric oxide (NO)-dependent vasodilator tone that opposes adrenergic vasoconstrictor activity in the intact dog. Circumflex flow (CxF) responses to randomized intracoronary microinjections (0.3 mL) of normal saline (NS), alkalinized saline (AS), intralipid (IL), adenosine (ADE, 17 micrograms), acetylcholine (ACh, 1.25 micrograms), ETO (6, 12, 60 micrograms), PRO (30, 60, 300 micrograms), and STP (75, 150, 750 micrograms) were quantified in eight isoflurane-anesthetized dogs with fixed ventricular rates (100 bpm). Injections were repeated during intravenous (IV) infusion (50 mg/kg + 1 mg.kg-1.min-1) of NG-nitro-L-arginine methyl ester (L-NAME). ADE and ACh transiently increased CxF to 305% +/- 20% (P < 0.001) and 310% +/- 29% (P < 0.001) of resting values, respectively. ETO had no effect, whereas PRO (300 micrograms) provoked small transient increases in CxF to 135% +/- 4% (P < 0.05) of control. Responses to STP (750 micrograms) were characterized by momentary decreases to 74% +/- 4% (P < 0.001), followed immediately by increases to 183% +/- 11% (P < 0.001) of resting values; NS AS, and IL had no effect. The momentary decreases with STP (750 micrograms) were significantly augmented during NO inhibition with CxF declining to 49% +/- 7% (P < 0.001) of resting values, whereas the secondary increase was unchanged. With L-NAME, CxF responses to ACh were attenuated to 32% +/- 3% (P < 0.001) of control, whereas responses to ADE, ETO, and PRO were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of nitric oxide inhibition on the coronary vasomotor responses to etomidate, propofol, and thiopental in anesthetized dogs. 806 46

1. We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of the vessels. Indomethacin (14 microM) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following endothelial removal. 3. Acetylcholine produced concentration-dependent relaxation of the vessels which was potentiated by indomethacin (14 microM). 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the contractile response to either noradrenaline or potassium chloride but abolished relaxation to acetylcholine. In addition, L-NAME abolished the affects of indomethacin on acetylcholine-induced relaxation and noradrenaline- and potassium chloride-induced contraction. 5. BWC755C attenuated noradrenaline and potassium chloride-induced contraction. This effect persisted in the presence of indomethacin. 6. In vessels pretreated with CHAPS, BW755C inhibited both noradrenaline and potassium chloride-induced contraction. In these vessels BW755C had no additional inhibitory effect to indomethacin on noradrenaline- and potassium-induced contraction. 7. Inhibition of nitric oxide synthase with L-NAME (100 microM) attenuated the effect of BW755C on noradrenaline- and potassium-induced contraction. 8. BW755C alone did not affect endothelium-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholine-induced relaxation. 9. BW755C did not affect endothelium-independent relaxation as assessed by the response to sodium nitroprusside in vessels with or without endothelium. 10. These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of renal arcuate arteries with noradrenaline and potassium chloride. A cyclooxygenase product which appears to be endothelium-independent and the other an endothelium dependent lipoxygenase product.
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PMID:Relative roles of nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries. 807 54

This study set out to identify the neurotransmitters involved in autonomic vasodilatation of the guinea pig uterine artery. Non-noradrenergic, paracervical neurons supplying this artery contain at least four neuropeptides: vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), dynorphin A (1-17) and somatostatin, probably in addition to acetylcholine. Transmural nerve stimulation of arterial segments precontracted with phenylephrine (3 x 10(-7) mol l-1 and treated with guanethidine (10(-6) mol l-1), produced relaxations which varied in form with the frequency of stimulation and the length of the pulse train. The relaxations were monophasic at low frequencies (< 2 Hz), and were biphasic at higher frequencies (> 5 Hz) and with longer pulse trains (> 50 pulses). Neither phase of the relaxations was reduced by hyoscine (10(-6) mol l-1), or by removal of the endothelium. The faster phase of the relaxations was selectively reduced (by 61%) during treatment with L-nitro-arginine methyl ester (L-NAME; up to 3 x 10(-5) mol l-1). This reduction was reversed by an excess of L-arginine, indicating that the fast relaxation was mediated by nitric oxide, possibly acting as a neurotransmitter. The slower phase of the neurogenic relaxation was preferentially reduced (by 43%) by the endopeptidase, trypsin (1-3 micrograms.ml-1). As VIP is the only currently identified peptide present in the paracervical neurons which causes vasodilatation, it is likely that VIP, or a closely-related peptide, is the transmitter responsible for the slow relaxation. Acetylcholine and an opioid peptide also seem to be released from the vasodilator neurons, but their effects were small, and may have been restricted to pre-synaptic sites. The slower neurogenic relaxations were inhibited by exogenous neuropeptide Y (68% reduction in amplitude), and were slightly potentiated by somatostatin (21% increase in amplitude). Therefore, endogenous stores of these peptides may also contribute to the sum effect of stimulating the paracervical vasodilator neurons. In conclusion, many different substances may act as autonomic co-transmitters from these pelvic vasodilator neurons.
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PMID:Co-transmission from autonomic vasodilator neurons supplying the guinea pig uterine artery. 809 24

Endothelium-derived relaxing factor-nitric oxide (EDRF-NO) has been studied in isolated, pulmonary resistance vessels from term fetal lambs at a fetal (21 +/- 0.2 mmHg) and neonatal (69 +/- 0.4 mmHg) PO2. Bradykinin dose dependently (0.1-100 nM) relaxed arteries and veins that had been precontracted with a thromboxane A2 analogue. Their response did not differ at low PO2, whereas the response of the arteries was greater at high PO2. Sodium nitroprusside was almost as potent as bradykinin on the arteries, but its action did not vary with PO2. Acetylcholine also relaxed the arteries at higher concentrations (0.1-100 microM). N omega-mono-methyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) (both at 100 microM) weakly contracted arteries at low PO2. The contraction to L-NAME, but not L-NMMA, increased with the PO2. In the arteries, L-NAME had no effect on bradykinin relaxation at low PO2, whereas it was an inhibitor at high PO2. Conversely, L-NMMA slightly inhibited bradykinin relaxation regardless of PO2. In the veins, L-NAME transiently increased basal tone and inhibited bradykinin relaxation at either PO2. Indomethacin (2.8 microM) had no effect on arteries at low PO2, whereas it was a constrictor at high PO2. No indomethacin constriction occurred in the veins. We conclude that fetal pulmonary resistance vessels possess an EDRF-NO relaxing mechanism that is stimulated by bradykinin. In the arteries, this mechanism is more effective at high PO2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:EDRF in pulmonary resistance vessels from fetal lamb: stimulation by oxygen and bradykinin. 816 Aug 41

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